Assessment of the Genetic Characteristics of a Generation Born during a Long-Term Socioeconomic Crisis.

BACKGROUND: A socioeconomic crisis in Russia lasted from 1991 to 1998 and was accompanied by a sharp drop in the birth rate. The main factor that influenced the refusal to have children during this period is thought to be prolonged social stress. METHODS: comparing frequencies of common gene variants associated with stress-induced diseases among generations born before, after, and during this crisis may show which genes may be preferred under the pressure of natural selection during periods of increased social stress in urban populations. RESULTS: In the "crisis" group, a statistically significant difference from the other two groups was found in rs6557168 frequency (p = 0.001); rs4522666 was not in the Hardy-Weinberg equilibrium in this group, although its frequency did not show a significant difference from the other groups (p = 0.118). Frequencies of VNTRs in SLC6A3 and MAOA as well as common variants rs17689918 in CRHR1, rs1360780 in FKBP5, rs53576 in OXTR, rs12720071 and rs806377 in CNR1, rs4311 in ACE, rs1800497 in ANKK1, and rs7412 and rs429358 in APOE did not differ among the groups. CONCLUSIONS: a generation born during a period of prolonged destructive events may differ from the rest of the gene pool of the population in some variants associated with personality traits or stress-related disorders.

The habenular volume and PDE7A allelic polymorphism in major depressive disorder: preliminary findings.

OBJECTIVES: The habenula is a brain structure implicated in depression, yet with unknown molecular mechanisms. Several phosphodiesterases (PDEs) have been associated with a risk of depression. Although the role of PDE7A in the brain is unknown, it has enriched expression in the medial habenula, suggesting that it may play a role in depression. METHODS: We analysed: (1) habenula volume assessed by 3-T magnetic resonance imaging (MRI) in 84 patients with major depressive disorder (MDD) and 41 healthy controls; (2) frequencies of 10 single nucleotide polymorphisms (SNPs) in PDE7A gene in 235 patients and 41 controls; and (3) both indices in 80 patients and 27 controls. The analyses considered gender, age, body mass index and season of the MRI examination. RESULTS: The analysis did not reveal habenula volumetric changes in MDD patients regardless of PDE7A SNPs. However, in the combined group, the carriers of one or more mutations among 10 SNPs in the PDE7A gene had a lower volume of the left habenula (driven mainly by rs972362 and rs138599850 mutations) and consequently had the reduced habenular laterality index in comparison with individuals without PDE7A mutations. CONCLUSIONS: Our findings suggest the implication of the PDE7A gene into mechanisms determining the habenula structure.

Prevalence of Common Alleles of Some Stress Resilience Genes among Adolescents Born in Different Periods Relative to the Socioeconomic Crisis of the 1990s in Russia.

Social stress is common among people and is considered one of the causes of the declining birth rate. Predisposition to stress and stress-induced disorders is largely determined genetically. We hypothesized that due to differences in stress resistance, carriers of different genetic variants of genes associated with stress resilience and stress-induced diseases may have dissimilar numbers of offspring under conditions of long-term social stress. To test this hypothesis, a comparative analysis of frequencies of seven common polymorphic regions [exon 3 variable number of tandem repeats (VNTR) of the DRD4 gene, rs4680 of COMT, STin2 VNTR and the 5-HTTLPR (rs774676466) insertion/deletion polymorphism of SLC6A4, rs4570625 of TPH2, rs6265 of BDNF, and rs258747 of NR3C1] was performed on standardized groups of randomly selected adolescents born before, during, and after severe socioeconomic deprivation (the crisis of the 1990s in Russia). There were significant differences in frequencies of "long" alleles of the DRD4 gene (p = 0.020, χ2 = 5.492) and rs4680 (p = 0.022, χ2 = 5.289) in the "crisis" group as compared to the combined "noncrisis" population. It is possible that the dopaminergic system had an impact on the successful adaptation of a person to social stress.

SIRT1 Allele Frequencies in Depressed Patients of European Descent in Russia.

Depressive disorder (DD) is a widespread mental disorder. Although DD is to some extent inherited, the genes contributing to the risk of this disorder and its genetic mechanisms remain poorly understood. A recent large-scale genome-wide association Chinese study revealed a strong association between the SIRT1 gene variants and DD. The aim of this study was to analyze the occurrence of heterozygote carriers and search for rare SNP variants of the SIRT1 gene in a cohort of DD patients as compared with a cohort of randomly selected members of the Russian population. The complete coding sequences of the SIRT1 gene from 1024 DNA samples from the general Russian population and from 244 samples from patients with DD were analyzed using targeted sequencing. Four new genetic variants of the SIRT1 were discovered. While no significant differences in the allele frequencies were found between the DD patients and the general population, differences between the frequencies of homozygote carriers of specific alleles and occurrences of heterozygous were found to be significant for rs2236318 (P < 0.0001), and putatively, rs7896005 (P < 0.05), and rs36107781 (P < 0.05). The study found for the first time that two new SNPs (i.e., 10:69665829 and 10:69665971) along with recently reported ones (rs773025707 and rs34701705), are putatively associated with DD. The revealed DD-associated SIRT1 SNPs might confer susceptibility to this disorder in Russian population of European descent.

BRCA1 gene mutations frequency estimation by allele-specific real-time PCR of pooled genomic DNA samples.

The frequencies of four mutations in the BRCA1 gene (185delAG, T300G, 4153delA, and 5382insC) were estimated in the Russian population. The mutations were analyzed in 7920 DNA samples obtained from randomly selected Novosibirsk citizens and 570 samples from breast cancer patients at Siberian hospitals. The mutations were detected by allele-specific real-time PCR. The mutation analysis was performed with pooled DNA samples to reduce the cost of the study. The 5382insC mutation was found in 20 of 7920 (0.25%) population DNA samples and in 14 of 570 (2.46%) breast cancer samples; the T300G mutation was detected in 4 population samples (0.05%) and in 2 breast cancer samples (0.35%); the 185delAG or 4153delA mutations were not identified in any of the 7920 samples and were detected in 1 (0.18%) breast cancer case each.